tbuckley/cabot-search huggingface dataset:
Point-of-Care Noninvasive Prediction of Liver-Related Events in Patients With Nonalcoholic Fatty Liver Disease
Authors: Mònica Pons, Jesús Rivera-Esteban, Mang M. Ma, Tracy Davyduke, Adèle Delamarre, Paul Hermabessière, Julie Dupuy, Grace Lai-Hung Wong, Terry Cheuk-Fung Yip, Grazia Pennisi, Adele Tulone, Calogero Cammà, Salvatore Petta, Victor de Lédinghen, Vincent Wai-Sun Wong, Salvador Augustin, Juan Manuel Pericàs, Juan G. Abraldes, Joan Genescà
Journal: Clinical Gastroenterology and Hepatology (2023)
Exposure to lung-migrating helminth protects against murine SARS-CoV-2 infection through macrophage-dependent T cell activation
Authors: Oyebola O. Oyesola, Kerry L. Hilligan, Sivaranjani Namasivayam, Nina Howard, Chad S. Clancy, Mingming Zhao, Sandra D. Oland, Kasalina N. Kiwanuka, Nicole L. Garza, Bernard A. P. Lafont, Reed F. Johnson, Katrin D. Mayer-Barber, Alan Sher, P’ng Loke
Journal: Science Immunology (2023)

Helminth endemic regions report lower COVID-19 morbidity and mortality. Here, we show that lung remodeling from a prior infection with a lung-migrating helminth, Nippostrongylus brasiliensis, enhances viral clearance and survival of human-ACE2 transgenic mice challenged with SARS-CoV-2 (SCV2). This protection is associated with a lymphocytic infiltrate, including increased accumulation of pulmonary SCV2-specific CD8+ T cells, and anti-CD8 antibody depletion abrogated the N. brasiliensis-mediated reduction in viral loads. Pulmonary macrophages with a type 2 transcriptional and epigenetic signature persist in the lungs of N. brasiliensis-exposed mice after clearance of the parasite and establish a primed environment for increased CD8+ T cell recruitment and activation. Accordingly, depletion of macrophages ablated the augmented viral clearance and accumulation of CD8+ T cells driven by prior N. brasiliensis infection. Together, these findings support the concept that lung-migrating helminths can limit disease severity during SCV2 infection through macrophage-dependent enhancement of antiviral CD8+ T cell responses.
Metabolic rewiring tunes dermal macrophages in staphylococcal skin infection
Authors: Aaron James Forde, Julia Kolter, Pascale Zwicky, Sebastian Baasch, Florens Lohrmann, Marleen Eckert, Vitka Gres, Simon Lagies, Oliver Gorka, Angelika S. Rambold, Joerg M. Buescher, Bernd Kammerer, Nico Lachmann, Marco Prinz, Olaf Groß, Edward J. Pearce, Burkhard Becher, Philipp Henneke
Journal: Science Immunology (2023)

The skin needs to balance tolerance of colonizing microflora with rapid detection of potential pathogens. Flexible response mechanisms would seem most suitable to accommodate the dynamic challenges of effective antimicrobial defense and restoration of tissue homeostasis. Here, we dissected macrophage-intrinsic mechanisms and microenvironmental cues that tune macrophage signaling in localized skin infection with the colonizing and opportunistic pathogen Staphylococcus aureus. Early in skin infection, the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) produced by γδ T cells and hypoxic conditions within the dermal microenvironment diverted macrophages away from a homeostatic M-CSF- and hypoxia-inducible factor 1α (HIF-1α)-dependent program. This allowed macrophages to be metabolically rewired for maximal inflammatory activity, which requires expression of Irg1 and generation of itaconate, but not HIF-1α. This multifactorial macrophage rewiring program was required for both the timely clearance of bacteria and for the provision of local immune memory. These findings indicate that immunometabolic conditioning allows dermal macrophages to cycle between antimicrobial activity and protection against secondary infections.
Interleukin 4-driven reversal of self-reactive B cell anergy contributes to the pathogenesis of systemic lupus erythematosus
Authors: Yaoyang Liu, Zhiguo Zhang, Zijian Kang, Xu-jie Zhou, Shujun Liu, Shicheng Guo, Qianmei Jin, Ting Li, Ling Zhou, Xin Wu, Yan-na Wang, Liangjing Lu, Yanran He, Fubin Li, Hong Zhang, Yuncai Liu, Huji Xu
Journal: Annals of the Rheumatic Diseases (2023)

Reactivation of anergic autoreactive B cells (BND cells) is a key aetiological process in systemic lupus erythematosus (SLE), yet the underlying mechanism remains largely elusive. This study aimed to investigate how BND cells participate in the pathogenesis of SLE and the underlying mechanism.A combination of phenotypical, large-scale transcriptome and B cell receptor (BCR) repertoire profiling were employed at molecular and single cell level on samples from healthy donors and patients with SLE. Isolated naïve B cells from human periphery blood were treated with anti-CD79b mAb in vitro to induce anergy. IgM internalisation was tracked by confocal microscopy and was qualified by flow cytometer.We characterised the decrease and disruption of BND cells in SLE patients and demonstrated IL-4 as an important cytokine to drive such pathological changes. We then elucidated that IL-4 reversed B cell anergy by promoting BCR recycling to the cell surface via STAT6 signalling.We demonstrated the significance of IL-4 in reversing B cell anergy and established the scientific rationale to treat SLE via blocking IL-4 signalling, also providing diagnostic and prognostic biomarkers to identify patients who are most likely going to benefit from such treatments.
Perfusability and immunogenicity of implantable pre-vascularized tissues recapitulating features of native capillary network
Authors: Dhavan Sharma, Archita Sharma, Linghao Hu, Te-An Chen, Sarah Voon, Kayla J. Bayless, Jeremy Goldman, Alex J. Walsh, Feng Zhao
Journal: Bioactive Materials (2023)

Vascularization is a key pre-requisite to engineered anatomical scale three dimensional (3-D) constructs to ensure their nutrient and oxygen supply upon implantation. Presently, engineered pre-vascularized 3-D tissues are limited to only micro-scale hydrogels, which meet neither the anatomical scale needs nor the complexity of natural extracellular matrix (ECM) environments. Anatomical scale perfusable constructs are critically needed for translational applications. To overcome this challenge, we previously developed pre-vascularized ECM sheets with long and oriented dense microvascular networks. The present study further evaluated the patency, perfusability and innate immune response toward these pre-vascularized constructs. Macrophage-co-cultured pre-vascularized constructs were evaluated in vitro to confirm micro-vessel patency and perturbations in macrophage metabolism. Subcutaneously implanted pre-vascularized constructs remained viable and formed a functional anastomosis with host vasculature within 3 days of implantation. This completely biological pre-vascularized construct holds great potential as a building block to engineer perfusable anatomical scale tissues.
Obesity-associated microglial inflammatory activation paradoxically improves glucose tolerance
Authors: John D. Douglass, Kelly M. Ness, Martin Valdearcos, Alice Wyse-Jackson, Mauricio D. Dorfman, Jeremy M. Frey, Rachael D. Fasnacht, Olivia D. Santiago, Anzela Niraula, Jineta Banerjee, Megan Robblee, Suneil K. Koliwad, Joshua P. Thaler
Journal: Cell Metabolism (2023)
Loss of CD4+ T cell-intrinsic arginase 1 accelerates Th1 response kinetics and reduces lung pathology during influenza infection
Authors: Erin E. West, Nicolas S. Merle, Marcin M. Kamiński, Gustavo Palacios, Dhaneshwar Kumar, Luopin Wang, Jack A. Bibby, Kirsten Overdahl, Alan K. Jarmusch, Simon Freeley, Duck-Yeon Lee, J. Will Thompson, Zu-Xi Yu, Naomi Taylor, Marc Sitbon, Douglas R. Green, Andrea Bohrer, Katrin D. Mayer-Barber, Behdad Afzali, Majid Kazemian, Sabine Scholl-Buergi, Daniela Karall, Martina Huemer, Claudia Kemper
Journal: Immunity (2023)

Arginase 1 (Arg1), the enzyme catalyzing the conversion of arginine to ornithine, is a hallmark of IL-10-producing immunoregulatory M2 macrophages. However, its expression in T cells is disputed. Here, we demonstrate that induction of Arg1 expression is a key feature of lung CD4+ T cells during mouse in vivo influenza infection. Conditional ablation of Arg1 in CD4+ T cells accelerated both virus-specific T helper 1 (Th1) effector responses and its resolution, resulting in efficient viral clearance and reduced lung pathology. Using unbiased transcriptomics and metabolomics, we found that Arg1-deficiency was distinct from Arg2-deficiency and caused altered glutamine metabolism. Rebalancing this perturbed glutamine flux normalized the cellular Th1 response. CD4+ T cells from rare ARG1-deficient patients or CRISPR-Cas9-mediated ARG1-deletion in healthy donor cells phenocopied the murine cellular phenotype. Collectively, CD4+ T cell-intrinsic Arg1 functions as an unexpected rheostat regulating the kinetics of the mammalian Th1 lifecycle with implications for Th1-associated tissue pathologies.
Real-world experience with ponatinib therapy in chronic phase chronic myeloid leukemia: impact of depth of response on survival and prior exposure to nilotinib on arterial occlusive events
Authors: Maymona G. Abdelmagid, Aref Al-Kali, Mark R. Litzow, Kebede H. Begna, William J. Hogan, Mirinal S. Patnaik, Shahrukh K. Hashmi, Michelle A. Elliott, Hassan Alkhateeb, Omer S. Karrar, Farah Fleti, Mohammed H. Elnayir, Candido E. Rivera, Hemant S. Murthy, James M. Foran, Mohamed A. Kharfan-Dabaja, Talha Badar, David S. Viswanatha, Kaaren K. Reichard, Naseema Gangat, Ayalew Tefferi
Journal: Blood Cancer Journal (2023)

Abstract We surveyed the performance of ponatinib, as salvage therapy, in a real-world setting of chronic phase chronic myeloid leukemia (CML-CP). Among 55 consecutive patients (median age 49 years) with relapsed/refractory CML-CP, 35 (64%) had failed ≥3 tyrosine kinase inhibitors (TKIs), 35 (64%) were pre-treated with nilotinib, and 14 (28%) harbored ABL1 T315I. At start of ponatinib (median dose 30 mg/day), 40 patients were already in complete hematologic (CHR), 4 in complete cytogenetic (CCyR), 3 in major molecular (MMR) remission, while 8 had not achieved CHR (NR). Ponatinib improved the depth of response in 13 (33%), 3 (75%), 2 (66%), and 4 (50%) patients with CHR, CCyR, MMR, and NR, respectively ( p = 0.02). At a median follow-up of 42 months, 13 (23%) deaths, 5 (9%) blast transformations, and 25 (45%) allogeneic transplants were recorded. Five/10-year post-ponatinib survival was 77%/58% with no significant difference when patients were stratified by allogeneic transplant ( p = 0.94), ponatinib-induced deeper response ( p = 0.28), or a post-ponatinib ≥CCyR vs CHR remission state ( p = 0.25). ABL1 T315I was detrimental to survival ( p = 0.04) but did not appear to affect response. Prior exposure to nilotinib was associated with higher risk of arterial occlusive events (AOEs; 11% vs 0%; age-adjusted p = 0.04). Ponatinib starting/maintenance dose (45 vs 15 mg/day) did not influence either treatment response or AOEs. Our observations support the use of a lower starting/maintenance dose for ponatinib in relapsed/refractory CML-CP but a survival advantage for deeper responses was not apparent and treatment might not overcome the detrimental impact of ABL1 T315I on survival. The association between prior exposure to nilotinib and a higher risk of post-ponatinib AOEs requires further validation.
Blood glucose variance measured by continuous glucose monitors across the menstrual cycle
Authors: Georgianna Lin, Rumsha Siddiqui, Zixiong Lin, Joanna M. Blodgett, Shwetak N. Patel, Khai N. Truong, Alex Mariakakis
Journal: npj Digital Medicine (2023)

Abstract Past studies on how blood glucose levels vary across the menstrual cycle have largely shown inconsistent results based on limited blood draws. In this study, 49 individuals wore a Dexcom G6 continuous glucose monitor and a Fitbit Sense smartwatch while measuring their menstrual hormones and self-reporting characteristics of their menstrual cycles daily. The average duration of participation was 79.3 ± 21.2 days, leading to a total of 149 cycles and 554 phases in our dataset. We use periodic restricted cubic splines to evaluate the relationship between blood glucose and the menstrual cycle, after which we assess phase-based changes in daily median glucose level and associated physiological parameters using mixed-effects models. Results indicate that daily median glucose levels increase and decrease in a biphasic pattern, with maximum levels occurring during the luteal phase and minimum levels occurring during the late-follicular phase. These trends are robust to adjustments for participant characteristics (e.g., age, BMI, weight) and self-reported menstrual experiences (e.g., food cravings, bloating, fatigue). We identify negative associations between each of daily estrogen level, step count, and low degrees of fatigue with higher median glucose levels. Conversely, we find positive associations between higher food cravings and higher median glucose levels. This study suggests that blood glucose could be an important parameter for understanding menstrual health, prompting further investigation into how the menstrual cycle influences glucose fluctuation.
Modeling and countering the effects of cosmic radiation using bioengineered human tissues
Authors: Daniel Naveed Tavakol, Trevor R. Nash, Youngbin Kim, Siyu He, Sharon Fleischer, Pamela L. Graney, Jessie A. Brown, Martin Liberman, Manuel Tamargo, Andrew Harken, Adolfo A. Ferrando, Sally Amundson, Guy Garty, Elham Azizi, Kam W. Leong, David J. Brenner, Gordana Vunjak-Novakovic
Journal: Biomaterials (2023)
Medical doctor apprenticeships are coming to the UK
Authors: Matthew David Morgan, Jahangir Alom, Elisha De-Alker, Sally Curtis
Journal: BMJ (2023)

The NHS has been under severe pressure for many years, exacerbated by substantial gaps in the healthcare workforce and complicated by inequities in healthcare access and outcomes. 1 In response, NHS England's long term workforce plan proposes to increase medical student numbers by 30% by 2028-29, including 850 medical doctor apprenticeships, and to double numbers by 2031.
CTLA-4 blockade induces a microglia-Th1 cell partnership that stimulates microglia phagocytosis and anti-tumor function in glioblastoma
Authors: Dan Chen, Siva Karthik Varanasi, Toshiro Hara, Kacie Traina, Ming Sun, Bryan McDonald, Yagmur Farsakoglu, Josh Clanton, Shihao Xu, Lizmarie Garcia-Rivera, Thomas H. Mann, Victor Du, H. Kay Chung, Ziyan Xu, Victoria Tripple, Eduardo Casillas, Shixin Ma, Carolyn O’Connor, Qiyuan Yang, Ye Zheng, Tony Hunter, Greg Lemke, Susan M. Kaech
Journal: Immunity (2023)
Overdiagnosis and too much medicine in a world of crises
Authors: Thomas Kühlein, Helen Macdonald, Barnett Kramer, Minna Johansson, Steven Woloshin, Kirsten McCaffery, John B. Brodersen, Tessa Copp, Karsten Juhl Jørgensen, Anne Møller, Martin Scherer
Journal: BMJ (2023)
Perianal and anal skin cancers treated with Mohs micrographic surgery and interdisciplinary care: Local recurrence rates and patient-reported outcomes
Authors: Shannon T. Nugent, Leela K. Raj, Cary B. Aarons, Nicole M. Saur, Stephen J. Kovach, John P. Fischer, Jeremy R. Etzkorn, Thuzar M. Shin, Cerrene N. Giordano, H. William Higgins, Joanna L. Walker, Christopher J. Miller
Journal: Journal of the American Academy of Dermatology (2023)
COVID-19 vaccine effectiveness against hospitalisation and death of people in clinical risk groups during the Delta variant period: English primary care network cohort study
Authors: Heather J. Whitaker, Ruby S.M. Tsang, Rachel Byford, Carole Aspden, Elizabeth Button, Praveen Sebastian Pillai, Gavin Jamie, Debasish Kar, John Williams, Mary Sinnathamby, Gemma Marsden, William H. Elson, Meredith Leston, Sneha Anand, Cecilia Okusi, Xuejuan Fan, Ezra Linley, Cathy Rowe, Silvia DArcangelo, Ashley D. Otter, Joanna Ellis, F.D. Richard Hobbs, Victoria Tzortziou-Brown, Maria Zambon, Mary Ramsay, Kevin E. Brown, Gayatri Amirthalingam, Nick J. Andrews, Simon de Lusignan, Jamie Lopez Bernal
Journal: Journal of Infection (2023)

COVID-19 vaccines have been shown to be highly effective against hospitalisation and death following COVID-19 infection. COVID-19 vaccine effectiveness estimates against severe endpoints among individuals with clinical conditions that place them at increased risk of critical disease are limited.
Re: Rakesh Heer, Rebecca Lewis, Thenmalar Vadiveloo, et al. A Randomized Trial of PHOTOdynamic Surgery in Non–muscle-invasive Bladder Cancer. NEJM Evid 2022;1:EVIDoa2200092
Authors: Jonathan Sussman, Badrinath Konety, Hamed Ahmadi
Journal: European Urology (2023)
M2 exosomes modified by hydrogen sulfide promoted bone regeneration by moesin mediated endocytosis
Authors: Yi-kun Zhou, Chun-shan Han, Zi-lu Zhu, Peng Chen, Yi-ming Wang, Shuai Lin, Liu-jing Chen, Zi-meng Zhuang, Yan-heng Zhou, Rui-li Yang
Journal: Bioactive Materials (2023)

Bone defects caused by trauma or tumor led to high medical costs and poor life quality for patients. The exosomes, micro vesicles of 30-150 nm in diameter, derived from macrophages manipulated bone regeneration. However, the role of hydrogen sulfide (H2S) in the biogenesis and function of exosomes and its effects on bone regeneration remains elusive. In this study, we used H2S slow releasing donor GYY4137 to stimulate macrophages and found that H2S promoted the polarization of M2 macrophages to increase bone regeneration of MSCs in vitro and in vivo. Moreover, we developed the H2S pre-treated M2 macrophage exosomes and found these exosomes displayed significantly higher capacity to promote bone regeneration in calvarial bone defects by re-establishing the local immune microenvironment. Mechanically, H2S treatment altered the protein profile of exosomes derived from M2 macrophages. One of the significantly enriched exosomal proteins stimulated by H2S, moesin protein, facilitated the exosomes endocytosis into MSCs, leading to activated the β-catenin signaling pathway to promote osteogenic differentiation of MSCs. In summary, H2S pretreated M2 exosomes promoted the bone regeneration of MSCs via facilitating exosomes uptake by MSCs and activate β-catenin signaling pathway. This study not only provides new strategies for promoting bone regeneration, but also provides new insights for the effect and mechanism of exosomes internalization.
Waning protection after vaccination and prior infection against COVID-19-related mortality over 18 months
Authors: Dominik Dietler, Fredrik Kahn, Malin Inghammar, Jonas Björk
Journal: Clinical Microbiology and Infection (2023)

Evidence on waning patterns in protection from vaccine-induced, infection-induced, and hybrid immunity against death is scarce. The aim of this study is to assess the temporal trends in protection against mortality.Population-based case-control study nested in the total population of Scania Region, Sweden using individual-level registry data of COVID-19-related deaths (<30 days after positive SARS-CoV-2 test) between 27 December 2020 and 3 June 2022. Controls were matched for age, sex, and index date. Conditional logistic regression was used to estimate the preventable fraction (PF) from vaccination (PFvac corresponding to vaccine effectiveness; ≥2 vaccine doses vs. 0 doses), prior infection (PFinf), and hybrid immunity (PFhybrid). PF was calculated as one minus odds ratio. Models were adjusted for comorbidities, long-term care facility residence, prior infection (for PFvac), country of birth, socio-economic conditions, and time since last vaccination (for PFinf).In total, 14 936 individuals (1440 COVID-19-related deaths and 13 496 controls) were included in the case-control analyses (45% females, median age: 84 years). PFvac was above 90% during the first month after vaccination, regardless of the number of vaccine doses. After 6 months, PFvac of two doses waned to 34% (95% CI: -30% to 66%). PFinf for people surviving a SARS-CoV-2 infection waned from 88% (-16% to 99%) 3 months after infection to 62% (34-79%) after 9 months. No differences in waning patterns in PFvac were seen between virus variants, gender, and age.Given the waning of protection against death, continuous surveillance of population immunity status, particularly among the most vulnerable population groups, could help to further fine-tune vaccination recommendations.
Lipid nanoparticle-mediated messenger RNA delivery for ex vivo engineering of natural killer cells
Authors: Stefania Douka, Lisa E. Brandenburg, Cristina Casadidio, Johanna Walther, Bianca Bonetto Moreno Garcia, Jan Spanholtz, Monica Raimo, Wim E. Hennink, Enrico Mastrobattista, Massimiliano Caiazzo
Journal: Journal of Controlled Release (2023)

Natural killer (NK) cells participate in the immune system by eliminating cancer and virally infected cells through germline-encoded surface receptors. Their independence from prior activation as well as their significantly lower toxicity have placed them in the spotlight as an alternative to T cells for adoptive cell therapy (ACT). Engineering NK cells with mRNA has shown great potential in ACT by enhancing their tumor targeting and cytotoxicity. However, mRNA transfection of NK cells is challenging, as the most common delivery methods, such as electroporation, show limitations. Therefore, an alternative non-viral delivery system that enables high mRNA transfection efficiency with preservation of the cell viability would be beneficial for the development of NK cell therapies. In this study, we investigated both polymeric and lipid nanoparticle (LNP) formulations for eGFP-mRNA delivery to NK cells, based on a dimethylethanolamine and diethylethanolamine polymeric library and on different ionizable lipids, respectively. The mRNA nanoparticles based on cationic polymers showed limited internalization by NK cells and low transfection efficiency. On the other hand, mRNA-LNP formulations were optimized by tailoring the lipid composition and the microfluidic parameters, resulting in a high transfection efficiency (∼100%) and high protein expression in NK cells. In conclusion, compared to polyplexes and electroporation, the optimized LNPs show a greater transfection efficiency and higher overall eGFP expression, when tested in NK (KHYG-1) and T (Jurkat) cell lines, and cord blood-derived NK cells. Thus, LNP-based mRNA delivery represents a promising strategy to further develop novel NK cell therapies.
Annexin <scp>A5</scp> inhibits mast cell activation via Allergin‐1 immunoreceptor
Authors: Mariana Silva Almeida, Satoko Tahara‐Hanaoka, Shohei Shibagaki, Kouta Niizuma, Kaori Hitomi, Yasuhiro Shinkai, Shiro Shibayama, Akira Shibuya
Journal: Allergy (2023)

The data that support the findings of this study are available from the corresponding author upon reasonable request. Appendix S1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
The International Association for the Study of Lung Cancer Pleural Mesothelioma Staging Project: Updated Modeling of Prognostic Factors in Pleural Mesothelioma
Authors: Andrea S. Wolf, Adam Rosenthal, Dorothy J. Giroux, Anna K. Nowak, Andrea Bille, Marc de Perrot, Hedy L. Kindler, David Rice, Isabelle Opitz, Valerie W. Rusch, Harvey I. Pass
Journal: Journal of Thoracic Oncology (2023)